It has been postulated that a possible cause of failure of radiation to produce local tumore control is the existence within tumors of hypoxic cells of reduced radiosensitivity. Fluosol infusion and hyperbaric oxyten breathing will be investigated as a means to overcome this problem by improving the oxygenation of tumor cells during radiation therapy. Theoretical considerations suggest that hyperbaric oxygen alone should be only minimally effective in improving the results of radiation therapy, as has been observed in many clinical trials. Oxygen moves into tissue primarily by diffusion. In order to increase the effective diffusion distance, the partial pressure of oxygen at the capillary level must be significantly increased. This can be accomplished only if sufficient oxygen can be carried in the blood not bound to hemoglobin, so that no unloading of oxygen from hemoglobin is necessary to supply tissue needs. Because of the limited solubility of oxygen in plasma this condition cannot be met with hyperbaric oxygen alone at pressures which are convenient and non-toxic. Fluosol, a perfluorochemical oxygen transport fluid and plasma expander, has been used as a blood substitute and to improve the oxygen carrying capacity of whole blood. In the presence of Fluosol, in concentrations well tolerated in man, the non-hemoglobin oxygen carrying capacity of blood will be sufficient at elevated oxygen pressure to overcome the oxygen buffering capacity of hemoglobin. Hyperbaric oxygen augmented by Fluosol should increase oxygen partial pressure at the capillary level, increase tumor oxygenation and thereby improve the results of radiation therapy. Preliminary animal studies support these predictions. Two specific clinical trials based on this hypothesis are proposed: 1) a phase I-II trial to investigate the safety and efficacy of the addition of Fluosol and hyperbaric oxygen breathing to radiation therapy in the treatment of advanced unresectable squamous cell carcinoma of the head and neck region, and 2) a phase I-II trial to investigate the safety and efficacy of the addition of FLuosol infusion and hyperbaric oxygen breathing to radiation therapy in the treatment of glioblastoma multiforme.